Spectrum of Cervical Cytological Lesions in Premenopausal and Postmenopausal Women

Background: Screening with Pap smear initially targets women with higher prevalence of high grade precancerous cervical lesions [Cervical Intraepithelial Neoplasia 2/3 (CIN2/CIN3)] women mostly in their third and fourth decade. But different conditions affect uterine cervix, including non neoplastic & neoplastic diseases, at different age. Thus, the Pap smears findings should vary in premenopausal & post menopausal groups. Methods: A prospective study of two years was conducted to screen Pap smears in women who were categorised as premenopausal age group <46 years & postmenopausal ≥46years. Result: A total of 6647 cases were analysed within age ranging from 18 to 85 years. 5369 (80.77%) patients were in premenopausal & 1278 (19.23%) in postmenopausal age group. Premenopausal group showed interpretation as “Negative for Intraepithelial Lesion or Malignancy” (NILM) in 97.56%. Here, two of the three cases of Squamous Cell Carcinoma (SCC) were of < 40 years. Postmenopausal age group showed maximum cases of Atypical Squamous Cells of Undetermined Significance (ASCUS), Low Grade Squamous Intraepithelial Lesion (LSIL) & SCC. Maximum cases of High-Grade Squamous Intraepithelial Lesion (HSIL) belonged to >60 years. Conclusion: It is suggested that the Pap screening should not be ceased, but be continued beyond 60 years of age. In premenopausal age, along with SIL, the possibility of malignancy should not be neglected & infections should also be paid more attention. Thus, irrespective of the age of female after 30 yrs, it is highly recommended for them to undergo PAP screening.

Annals of Pathology and Laboratory Medicine, Vol. 4, Issue 6, November-December, 2017 years, from July 2015 to June 2017. A total of 6647 cases were selected who were above 18 years and sexually active for > 3 years.
Relevant history, presenting complaints (like discharge per vaginum, bleeding per vaginum, pain in lower abdomen, backache) and examination findings including per speculum findings were entered in a proforma.
On the day of procuring Pap smear care was taken that no local douche, antiseptic cream and no local internal examination was done. The patient was placed in dorsal lithotomy position. After proper positioning, gently a sterile Cusco's bivalve speculum was introduced through vagina and cervix was visualized. The longer projection of the Ayre's spatula was placed in the cervix near squamo-columnar junction and rotated through 360°. The cellular material thus obtained was quickly, but gently smeared on a clean glass slide. The glass slide was then immediately put into the Coplin jar containing 95% ethyl alcohol as a fixative. The prepared smears were then stained according to Papanicolaou's technique. The cytological interpretation of the smears was made according to The Bethesda System 2014.

Result
Total 6647 patients fulfilling the inclusion criteria in the above mentioned period with ages ranging from 18 to 85 years were analysed. Out of them, 5369 (80.77%) patients were in premenopausal & 1278 (19.23%) in postmenopausal age group. The most common presenting complaint was discharge per vaginum, present in 5296 (77.68%) patients. Post menopausal bleeding was the chief complaint in 14 patients (0.21%). Only 5 (0.08%) patients presented with post-coital bleeding. Most common per speculum finding was white discharge at external os in 5127(77.13%) patients. Ulcerative or fungating growth was observed in only 5 patients (0.08%).
The categorization of all the patients according to The Bethesda System 2014 is shown in Table 1. Total 180 Premenopausal Age Group: Of the smears obtained from 5369 premenopausal patients of this study, 96 (1.79%) were unsatisfactory. The major finding in them was obscuration of the cellular details due to either dense acute inflammatory infiltrate or blood. The majority of the smears (5238 -97.56% of premenopausal age group) belonged to NILM category, of them the maximum (2418 -46.16% of this age group) had interpretation as 'Inflammatory smear without underlying pathology'. Most common interpretation in organism subcategory (1428 -26.6% of premenopausal age group). Only 0.65% of patients showed epithelial abnormalities. In this group, most cases of HSIL (six out of 11) fell between 30 -39 years age, this decade was also the second most common affected age group for it overall. Two of the 3 cases of SCC of this group were < 40 years of age. (Table2) One case each of Adenocarcinoma & ASC-H were found.

Discussion
Various conditions can affect uterine cervix, including non neoplastic & neoplastic diseases at different age. The incidence of carcinoma cervix peaks at the age of 55 years in India. [9] It is preceded by premalignant lesions by approximately 10-20 years. [9] However, the infectious conditions are known to be more common in reproductive age group. All of these are found very well by Pap smears.
The recent studies in South India have found NILM inflammatory smears to be most common finding in Pap smears, in approximately 70-90% of cases (Table 3). [10], [12][13][14], [16][17][18][19][20] Present study is concordant with them. Only few found them to be less common, second only to NILM Normal smear. [11], [15] The age wise distribution of these cases has been done less frequently than in the premalignant & malignant lesions. Those who have studied the same, found inflammatory smears most common in 30-40 age group, [12], [14], [15] one of them mentioning 20 -40 years as common affected group in cytology. [13] Present study also finds NILM, Inflammatory smears to be common in Premenopausal women.
Most of these recent works found fungal infection morphologically consistent with Candida species as the most common organism associated with specific infection, [12][13][14][15], [17], [19] followed by Bacterial Vaginosis in few, [11], [16], [18] similar to the present work. Only a single work shows Trichomonas vaginalis as the most common organism. [10] Chronic lymphocytic cervicitis (follicular cervicitis) is known to be more common and more likely to be detected in Postmenopausal women, [21] complying finding seen in present work.
The national guideline for cervical cancer screening in India advocates screening of women between 30 years to 59 years of age. [9] We found 7 of the 240 women (2.92%) of ≥60 years have Cervical Intraepithelial Neoplasia 2 (CIN2) or worse lesions, the rate which is almost 12.7 times that of 0.23% in 18 -59 years(15 of 6407) . Sixty-four percent of the CIN 2 or worse lesions at ages over 50 years were detected in women with previously negative smears by Blanks RG et al. [22] In present study the overall epithelial abnormalities were also more common in ≥ 60 years age group (12 of 240 cases -5%) against only 1.05%(67 of 6407) in the rest (Table 2). Thus, it is suggested that screening should be continued for women ≥60 years of age as well, even if having a negative cytology history. Large scale studies of Pap smear aiming the same age group in different regions of the country should be preformed.
We found 11 cases of HSIL in premenopausal & postmenopausal groups each, majority being ≥60 years age and second most affected age group is 30-39 years ( Table 2). Of the recent studies, maximum HSIL cases in 40-50 years, [12], [15], [19] & in ≥50 years were found in three each. [13], [14], [18] Most of LSIL belonged to 40 -49 years (perimenopausal age), concordant with two recent works; [12], [14] whereas maximum affected group of 50-60, [13], [18] & 30-40 was seen in two studies each (Table 6). [15], [19]s As mentioned by Bethesda, ASCUS was the most common epithelial abnormality reported here as well, with 50-59 years common age. However, most of the other studies found it to be maximum in 41-50 years. [13], [15], [19] Out of the remaining studies, one each have found maximum ASCUS cases in same age group(50-59 years), older (≥60 years) [18] & younger (30-40 years). [14] The percentage of interpretation of SCC by PAP smears in South Indian studies in these two years is ranging from 0 to 1.8%, present one has 0.14% (9 cases) lying within the range. The range of age in India having maximum cervical cancer incidence is 55-59 years. [23] Same finding is seen in the above mentioned studies, [12][13], [15], [18][19] but in our work it was 4 th decade (perimenopausal age) with two cases younger than 35years. These younger cases constituted 22.22% of all SCC cases. Recently the proportion of younger women being affected by SCC is increasing worldwide, accounting for about 25% of all patients in the US. [24] Adenocarcinoma of cervix is the least interpreted category in the studies in Table 3, though the incidence has been increasing world over, followed by AGUS & ASC -H. Present work shows interpretation as AGUS -two cases, Adenocarcinoma & ASC-H one case each. Symptoms of curdy discharge & foul smelling thin white discharge per vaginum correlated well with Pap interpretation of Candidiasis & Bacterial vaginosis respectively. Per speculum finding in five of nine cases of SCC cervix was ulcerative/ fungating growth, in rest of the cases history of post coital bleeding & post menopausal bleeding was present in two each.

Conclusion
From this work it is suggested that the Pap screening should not be ceased, but continued beyond 60 years of age. In premenopausal age, along with SIL, identification of malignancy & infection should also be paid more attention, so as to curb their mortality & morbidity respectively. Thus, irrespective of the age of female after 30 yrs, it is highly recommended for them to undergo Pap screening with follow up whenever required.